Identification of differential biological mechanisms between pregnancy and postpartum in Rheumatoid Arthritis

Abstract

Pregnancy in Rheumatoid Arthritis (RA) provides a unique model to study the biological mechanisms of the disease. In RA pregnancy, there is generally a transitory interruption of disease activity that is resumed after delivery. Consequently, the study of the molecular patterns associated with changes in disease activity during pregnancy could provide essential information on the main biologic pathways in the disease. Here we profile the transcriptomes of 8,604 high quality peripheral blood mononuclear cells (PBMCs) with sc-RNAseq from two RA women at the 30th week of gestation and at the 8th week of postpartum. PBMCs were studied after in vitro culture for 48 hours with and without T cell stimulation. The present study is the first single-cell atlas of PBMCs of RA during pregnancy and postpartum. An initial cell clustering analysis divided the cells into NK and unstimulated T cells, stimulated T cells, myeloid cells and B cells. These clusters could be further subdivided into 35 highly specific clusters. We detected an effectorness gradient in the unstimulated T cell compartment. In postpartum, cell composition analysis revealed an increase in unstimulated resting naïve T cells and GZMA+ GNLY+ producing CD8+ T cells. In stimulated cells, the analysis revealed an increase in activated T central memory cells with high ribosomal content and recently activated naïve T cells. In cells from pregnancy, we found an immune resistance to cell stimulation in CD14+ monocytes and CD16+ CD56dim NKs. Finally, differential gene expression between the different cell clusters revealed genes related possibly associated to modulation of disease during pregnancy. Also, genes that could be involved in pregnancy and oncogenesis and genes involved in RA and preeclampsia.

Date of Award	25 Jan 2022
Original language	English
Supervisor	Sara Marsal Barril (Director), Frauke Förger (Director) & Monika Ostensen (Director)